Exploring the Potential Utility of Pet Dogs With Cancer for Studying Radiation-Induced Immunogenic Cell Death Strategies

Radiotherapy serves as a foundational pillar for the therapeutic management of diverse solid tumors through the generation of lethal DNA damage and induction of cell death. While the direct cytotoxic effects of radiation therapy remain a cornerstone for cancer management, in the era of immunooncology there is renewed and focused interest in exploiting the indirect bystander activities of radiation, termed abscopal effects. In radioimmunobiologic terms, abscopal effects describe the radiotherapy-induced regression of cancerous lesions distant from the primary site of radiation delivery and rely upon the induction of immunogenic cell death and consequent systemic anticancer immune activation. Despite the promise of radiation therapy for awaking potent anticancer immune responses, the purposeful harnessing of abscopal effects with radiotherapy remain clinically elusive. In part, failure to fully leverage and clinically implement the promise of radiation-induced abscopal effects stems from limitations associated with existing conventional tumor models which inadequately recapitulate the complexity of malignant transformation and the dynamic nature of tumor immune surveillance. To supplement this existing gap in modeling systems, pet dogs diagnosed with solid tumors including melanoma and osteosarcoma, which are both metastatic and immunogenic in nature, could potentially serve as unique resources for exploring the fundamental underpinnings required for maximizing radiation-induced abscopal effects. Given the spontaneous course of cancer development in the context of operative immune mechanisms, pet dogs treated with radiotherapy for metastatic solid tumors might be leveraged as valuable model systems for realizing the science and best clinical practices necessary to generate potent abscopal effects with anti-metastatic immune activities.